Nature 387, 188 - 191 (08 May 1997); doi:10.1038/387188a0

Decay characteristics of HIV-1-infected compartments during combination therapy

Alan S. Perelson, Paulina Essunger, Yunzhen Cao^*, Mika Vesanen^*, Arlene Hurley^*, Kalle Saksela^†, Martin Markowitz^* & David D. Ho^*

Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA
^* Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, New York 10016, USA
^† Institute of Medical Technology, University of Tampere, Tampere, Finland

Analysis of changes in viral load after initiation of treatment with potent antiretroviral agents has provided substantial insight into the dynamics of human immunodeficiency virus type 1 (HIV-1)^1–3. The concentration of HIV-1 in plasma drops by 99% in the first two weeks of treatment owing to the rapid elimination of free virus with a half-life (t _1/2) of 6 hours and loss of productively infected cells with a t _1/2 of 1.6 days³. Here we show that with combination therapy this initial decrease is followed by a slower second-phase decay of plasma viraemia. Detailed mathematical analysis shows that the loss of long-lived infected cells (t _1/2of^1–4 weeks) is a major contributor to the second phase, whereas the activation of latently infected lymphocytes (t _1/2 of 0.5–2 weeks) is only a minor source. Based on these decay characteristics, we estimate that 2.3–3.1 years of a completely inhibitory treatment would be required to eliminate HIV-1 from these compartments. To eradicate HIV-1 completely, even longer treatment may be needed because of the possible existence of undetected viral compartments or sanctuary sites.

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